Hydration of Thiourea and Mono-, Di-, and Tetra- N -Alkylthioureas at Infinite Dilution: A Thermodynamic Study at a Temperature of 298.15 K

Published: October 20, 2011

r 2011 American Chemical Society 4778 dx.doi.org/10.1021/je2007742 | J. Chem. Eng. Data 2011, 56, 4778–4785

ARTICLE

pubs.acs.org/jced

Hydration of Thiourea and Mono-, Di-, and Tetra-N-Alkylthioureas atInfinite Dilution: A Thermodynamic Study at a Temperature of 298.15 KElena Badea† and Giuseppe Della Gatta*

Department of Chemistry IFM, University of Turin, via P. Giuria 9, 10125 Torino, Italy

Mazgorzata J�o�zwiak

Faculty of Chemistry, Physical Chemistry Department, University of y�od�z, ul. Pomorska 165, 90-236 y�od�z, Poland

Concetta Giancola

Department of Chemistry, University Federico II of Naples, Complesso Universitario diMonte S. Angelo, Via Cintia, 80126Napoli, Italy

ABSTRACT: Molar enthalpies of solution in water, ΔsolHm, of thiourea, methylthiourea, ethylthiourea, dimethyl-1,3-thiourea,diethyl-1,3-thiourea, and tetramethyl-1,1,3,3-thiourea were measured at T = (296.84, 302.45, and 306.89) K by isothermalcalorimetry. Experimental results were used to derive molar enthalpies of solvation at infinite dilution (i.d.), ΔsolvHm

∞, changes inheat capacity due to the solution process, ΔsolCp,m

∞ , and partial molar heat capacities at i.d., Cp,2∞ , at T = 298.15 K. The methylene

group contributions to the enthalpy of solvation and partial molar heat capacity were �4.5 kJ 3mol�1 and 88.5 J 3K�1

3mol�1,

respectively, in good agreement with our earlier data for N-alkylureas and the literature data for various homologous series of alkyl-substituted compounds. The contributions of the functional groups to both ΔsolvHm

∞ and Cp,2∞ were derived by employing additive

schemes and compared with our earlier data for urea and corresponding N-alkylureas. Hydration behavior at the i.d. of thiourea,urea, and corresponding N-alkyl derivatives were compared and discussed.

’ INTRODUCTION

Biophysical structures achieve their spatial organization andfunctional properties in aqueous milieu through competinghydrophilic and hydrophobic interactions which rule most ofbiophysical processes such as protein folding/unfolding, bio-membrane formation, lipid aggregation, selective recognition,in situ sensing of biological molecules, and so forth. Hydrophobicand hydrophilic moieties of biomolecules play therefore a crucialrole in both the self-assembly and functionality of biomolecules.The thermodynamic studies of the hydrophobic effect initiatedby Frank and Evans1 in 1945 and continued by Kautzmann2

showed that the entropic mechanism for association of nonpolarmoieties is central for protein folding and stability. To betterunderstand the complex interactions of biomolecules with theirenvironment, the hydration of small model molecules has thenbeen extensively studied.3�7 In this context, properties andhydration of urea and its N-alkyl derivatives, as small modelhydrophilic solutes, but also denaturants for proteins, have beenwidely investigated8�11 in the past decade, while thiourea andN-alkylthioureas have been far less explored. However, greatattention has been given to thiourea and its derivatives as enzymeinhibitors, in particular of HIV-1 reverse transcriptase,12 potentialreceptors and ionophores for heavy metal cations,13 and buildingblocks for anion receptors.14,15 It was shown that hydrogen-bondingability of the functional group�N(H)�C(=S)�N(H)� can bemodulated by the insertion of hydrophobic alkyl substituents.16,17

Moreover, the topography of hydrophobic moieties is expected toplay an important role in determining their bonding/hydration

as we found for urea and its N-alkyl derivatives.18,19 As aconsequence, thiourea and its derivatives are widely utilized inthe field of molecular recognition,20,21 while their employ-ment in both crystal assembly and functionalization, as wellas for the construction of nanostructured materials, is nowexplored.22 This paper reports the results of a study on thethermodynamics of hydration at infinite dilution (i.d.) ofthiourea, TU, and some of its N-alkylderivatives, namely,methylthiourea, MMTU, ethylthiourea, METU, dimethyl-1,3-thiourea, D(1,3)MTU, diethyl-1,3-thiourea, D(1,3)ETU, andtetramethyl-1,1,3,3-thiourea, T(1,1,3,3)MTU, as a continua-tion of our investigations on solute�solvent interactions ofurea and its mono-, di-, tri-, and tetrasubstituted N-alkylderivatives.14,15 Thiourea enthalpies and entropies of both fusionand sublimation23 and heat capacities in the solid state24 werepreviously reported. In this paper we conclude the thermody-namic characterization of thiourea and N-alkyl derivatives byproviding the hydration enthalpy and partial molar heat capacity,as well as the corresponding contributions of both polar andapolar moieties. A comprehensive picture of their thermodynamiccycle including fusion, sublimation, vaporization, and hydration isthus available.

Special Issue: Kenneth N. Marsh Festschrift

Received: July 22, 2011Accepted: October 3, 2011

4779 dx.doi.org/10.1021/je2007742 |J. Chem. Eng. Data 2011, 56, 4778–4785

Journal of Chemical & Engineering Data ARTICLE

’EXPERIMENTAL SECTION

Materials. Thiourea, TU (mass fraction purity 0.99), methyl-thiourea,MMTU (mass fraction purity 0.97), ethylthiourea,METU(mass fraction purity 0.99), dimethyl-1,3-thiourea, D(1,3)MTU(mass fraction purity 0.99), diethyl-1,3-thiourea, D(1,3)ETU(mass fraction purity 0.98), and tetramethyl-1,1,3,3-thioureaT(1,1,3,3)MTU (mass fraction purity 0.98) were from Aldrich.All compounds, except D(1,3)MTU, were purified by severalsuccessive crystallizations from either absolute ethanol (Flukapuriss, mass fraction purity >0.998) or (ethanol + water)solutions. The purification of T(1,1,3,3)MTU also includedsublimation under vacuum. D(1,3)MTU was purified by recrys-tallization from anhydrous tetrahydrofuran (Sigma-Aldrich, massfraction purity >0.999) and slowly precipitated by the addition ofdiisopropyl ether (Sigma-Aldrich, ACS reagent, mass fractionpurity >0.99) to suppress the supercooling effect. All compoundswere then dried to constant mass under reduced pressure at roomtemperature. Infrared spectra showed no traces of water in any ofthe purified compounds. Their final purity was always better than0.995 mass fraction, as determined by the differential scanningcalorimetry (DSC) peak profile method.23,25

Hexane, cyclohexane (Sigma-Aldrich, mass fraction purity>0.99), and urea (standard reference material from NationalBureau of Standards) were employed in the calibration tests ofthe calorimeter without any further purification. Deionizedbidistilled water HPLC grade from Sigma-Aldrich was used forsolution preparation.Calorimetric Measurements. Enthalpies of solution,ΔsolHm,

in water were measured at T = (296.84, 302.45, and 306.89) Kwith a CRMT-SETARAM rotating calorimeter (Tian-Calvettype). A glass ampule containing the sample was broken in a100 mL cell, as already described.26 The calibration tests weremade by the Joule effect, using the calibration cell with a 1000Ωconstantan resistance supplied by SETARAM and by determin-ing both the standard enthalpy of mixing of (hexane +cyclohexane)27 and enthalpy of dilution of aqueous solutions ofurea.28 A conversion factor of (7.36 ( 0.04) 10�5 J 3mm�1

3 s�1

was obtained in the experimental temperature range. Two out ofthree calibration tests were made using the same procedure asfor sample measurements. As a consequence, the intrinsicuncertainty associated with each measurement of solutionenthalpy corresponds in principle to that of the conversionfactor. The temperature was kept constant to( 0.05 K as fromthe calibration made with certified thermocouples kindlysupplied by the National Institute of Metrological Research(INRiM) in Turin. Three to four measurements of enthalpy ofsolution at different concentrations were performed for eachsample. The final concentration of the solutes was in the range(0.1 to 2) 3 10

�2 mol 3 kg�1.

’RESULTS AND DISCUSSION

Enthalpy of Solution at Infinite Dilution (i.d.). Enthalpies ofsolution at i.d. at the three experimental temperatures wereobtained by linear extrapolation to m = 0 of each set of data(Tables 1 and 2). The extrapolated molar enthalpies of solutionwere then fitted as a linear function of temperature:

ΔsolH∞m ¼ a þ bðT � 298:15Þ ð1Þ

where a =ΔsolHm∞ at T = 298.15 K (Table 2). The value obtained

for thiourea is in very good agreement with that previously

reported by Taniewska-Osi�nska and Pazecz.29 To the best ofour knowledge, no previous data for the solution process ofN-alkylthioureas are reported in the literature.Enthalpy of Solvation. The molar enthalpy of solvation,

ΔsolvHm∞, corresponding to the transfer of 1 mol of solute from

the ideal gaseous phase to aqueous solution at i.d. was derived bycombining molar enthalpy of solution at i.d., ΔsolHm

∞, andstandard molar enthalpy of sublimation, ΔsubHm

o , at 298.15 K:

ΔsolvH∞m ¼ ΔsolH

∞m �ΔsubH

om ð2Þ

The enthalpies of solvation at 298.15 K for thiourea and the fiveN-alkylthioureas together with the enthalpies of solution andsublimation23 used for their derivation are presented in Table 3,columns 2 to 4. The enthalpies of solvation for urea andcorresponding N-alkylureas obtained by us18,19 are reported forcomparison (column 6). ΔsolvHm

∞ values progressively increaseas a function of the alkyl chain length, displaying slightly highervalues than those of N-alkylureas, except T(1,1,3,3)MTU. Thisbehavior appears in agreement with the fact that thiourea andsubstituted thioureas have slightly higher dipole moments [(0.1to 0.3) D units] than urea and substituted ureas as reported byKumler and Fohlen.30 These authors also show thatN-alkylureasandN-alkylthioureas have dipole moments about 1 D unit higherthan those of simple amides and ascribed this to the greaterresonance energy of the two equivalent resonating forms with theseparation of charge. Thiourea's moment, higher than for ureaand in apparent contradiction with the electronegativity values ofsulfur and oxygen atoms, was later explained by a quantummechanical study by Orita et al.31 and then confirmed by an abinitio molecular orbital theory study by Weiqun et al.32 Bothpapers concluded that, in contrast to urea, the C�N bond isenhanced, while the polarity of C�S bond increases. It was alsoshown that, in spite of the common view that�S 3 3 3H bonds areweaker than �O 3 3 3H bonds, the total interaction energies arelikely the same in the region of carbonyl and thyonil groups.33

This feature is in agreement with an enhanced bonding ability ofthe sulfur atom brought about by the weakening of the C�Sbond mentioned above.As alkyl groups substitute the H atoms into thiourea, the

hydrophobic character of the molecule and its nitrogen regionprogressively increases as a function of the number of alkylcarbon atoms, and the solvation enthalpy becomesmore exother-mic, as previously reported for ureas.18,19 In Figure 1, a lineardependence of the solvation enthalpy on the number of C atomsof alkyl substituents for bothN-alkylthioureas andN-alkylureas isdepicted. The slopes, representing the solvation enthalpy of themethylene group, were (�4.5 ( 0.7) kJ 3mol�1 and (�3.0 (0.4) kJ 3mol�1,15 respectively. ΔsolvHm

∞ [CH2] for thioureasappears thus in reasonable agreement with earlier results forvarious series of homologous alkyl compounds.3,6,7,26,34�36

T(1,1,3,3)MTU was not considered for linearization since itssolvation enthalpy strongly deviates from the linear plot (Figure 1).The considerably low value of ΔsolvHm

∞ [T(1,1,3,3)MTU]should be attributed to both the steric hindrance provoked bybulky methylene groups and the intrinsic nitrogen atom inabilityto form hydrogen bonds with water. In fact, the hydrationscheme reported for thiourea indicates a maximum number ofonly four water molecules directly bound to thiourea since thetrans-NH bonds are not able to disrupt the water�water bonds, asituation different from that encountered in urea which binds fivewater molecules.31 Ab initio studies on the interactions of water



with T(1,1,3,3)MTU and T(1,1,3,3)MU concluded that thenitrogen atom of T(1,1,3,3)MTU is no longer able to interactwith the hydrogen atom of water, while the nitrogen atom ofT(1,1,3,3)MU still form a hydrogen bond with water. None-theless, in the neighborhood of the carbonyl/thyonil group the

total T(1,1,3,3)MU�water and T(1,1,3,3)MTU�water ener-gies are nearly identical.33

The contribution of the functional group (FG) to the solvationenthalpy ofN-alkylthioureas at T = 298.15 K was derived using asimple additivity scheme based on the subtraction from the

Table 1. Experimental Molar Enthalpies of Solution in Water, ΔsolHm, for Thiourea and Five N-Alkylthioureas at T = (296.84,302.45, and 306.89) K for Different Molality, m, Valuesa

m ΔsolHm m ΔsolHm

compound 10�3 mol 3 kg�1 kJ 3mol�1 compound 10�3 mol 3 kg

�1 kJ 3mol�1

TU T = 296.84 K METU T = 296.84K

6.95 22.65 1.16 24.43

9.10 22.55 2.31 24.50

9.47 22.48 2.96 24.71

11.58 22.59 4.01 24.75

T = 302.45 K T = 302.45K

4.86 22.84 1.94 24.65

7.52 22.80 2.88 24.62

9.60 22.86 3.45 24.48

T = 306.89 K 3.63 24.64

2.76 22.95 T = 306.89K

5.59 22.80 2.53 25.22

5.82 22.88 13.62 25.24

12.47 22.91 17.10 25.20

MMTU T = 296.84 K D(1,3)MTU T = 296.84K

6.76 22.78 10.77 13.74

7.95 22.92 12.90 14.20

8.84 22.74 16.63 13.65

10.90 22.89 19.30 14.05

T = 302.45 K T = 302.45K

7.80 23.34 6.02 14.41

10.34 23.27 6.50 14.25

11.60 22.54 9.58 14.21

T = 306.89 K T = 306.89K

8.96 23.15 2.97 15.32

11.09 23.20 3.75 15.28

11.71 23.10 8.97 15.34

D(1,3)ETU T = 296.84 K T(1,13,3)MTU T = 296.84K

6.94 15.28 1.90 15.94

8.45 15.24 3.40 15.80

9.73 15.37 5.67 15.90

T = 302.45 K T = 302.45K

6.20 16.53 2.67 17.21

8.49 16.32 3.62 17.30

13.50 16.42 4.09 17.22

5.78 17.18

T = 306.89 K T = 306.89K

8.05 17.66 2.87 18.24

8.25 17.61 3.92 18.22

10.47 17.61 4.29 18.18

5.40 18.04a For measurement uncertainty, see the Calorimetric Measurements section.



experimental ΔsolvHm∞ of each compound the sum of solvation

enthalpies of the alkyl groups in the molecule:

ΔsolvH∞m ½FG� ¼ ΔsolvH

∞m ½N-alkylthiourea� � ∑ΔsolvH

∞m ½alkylgroup�

ð3Þ

where the enthalpy of solvation of the methylene group (�4.5kJ 3mol�1) is from this paper and that of the methyl group(�8.28 kJ 3mol�1) is from Makhatadze and Privalov.37

ΔsolvHm∞ [FG] values listed in Table 4 are practically

identical for monoalkylthioureas and 1,3-dialkylthioureas,unlike monoalkylureas and 1,3-dialkylureas, and more nega-tive. These results are consistent with a prevailing role of thesulfur atom of the thiocarbonyl in the hydrophilic hydration ofthioureas. By contrast, N-alkylureas display ΔsolvHm

∞[FG]values progressively lower from mono-, to di-1,3-, di-1,1,-,tri-1,1,3-, and tetra-1,1,3,3-alkylderivatives, suggesting a sig-nificant and modulated by alkyl groups topography contribu-tion of the nitrogen atom to the hydrophilic hydration.19

The enthalpy of solvation of the [N�CS�N] group, account-ing for the hydrogen bonds in the thyonyl group region only, is

Table 2. Molar Enthalpies of Solution at Infinite Dilution in Water, ΔsolHm∞, for Thiourea and Five N-Alkylthioureas at T =

(296.84, 302.45, and 306.89) K, and Their Interpolated Values at 298.15 K from eq 1

ΔsolHm∞a/ kJ 3mol�1

compound Nb T = 296.84 K Nb T = 302.45 K Nb T = 306.89 K T = 298.15 K

TU 4 22.70 ( 0.23 3 22.81 ( 0.09 4 22.89 ( 0.08 22.73 ( 0.19

22.57c

MMTU 4 22.69 ( 0.29 3 22.98 ( 0.59 4 23.23 ( 0.36 22.76 ( 0.39

METU 4 24.28 ( 0.09 4 24.74 ( 0.20 3 25.23 ( 0.03 24.38 ( 0.13

D(1,3)MTU 4 13.81 ( 0.73 3 14.59 ( 0.28 3 15.28 ( 0.04 13.99 ( 0.62

D(1,3)ETU 3 15.04 ( 0.31 3 16.51 ( 0.26 3 17.73 ( 0.16 15.38 ( 0.30

T(1,1,3,3)MTU 3 15.90 ( 0.15 4 17.30 ( 0.10 4 18.43 ( 0.04 16.23 ( 0.14aData in columns 3, 5, and 7 are linearly extrapolated values atm = 0 with their uncertainties at a 95 % confidence level. Data in column 8 from eq 1 andassociated uncertainties are calculated by the error propagation rule. bNumber of experimental determinations. cReference 29.

Table 3. Molar Enthalpies of Solvation in Water at Infinite Dilution at T = 298.15 K of Thiourea and N-Alkylthioureas fromEquation 2 Compared with Urea and Corresponding N-Alkylureas

ΔsolHm∞ ΔsubHm

o a ΔsolvHm∞ ΔsolvHm

∞

compound kJ 3mol�1 kJ 3mol�1 kJ 3mol�1 compound kJ 3mol�1

TU 22.73 ( 0.19 112.0 ( 2 �89.3 ( 2 U �81.8 ( 0.6b

MMTU 22.76 ( 0.39 112.9 ( 3 �90.1 ( 3 MMU �85.0 ( 0.5b

METU 24.38 ( 0.13 118.8 ( 5 �94.4 ( 5 MEU �89.0 ( 1.3b

D(1,3)MTU 13.99 ( 0.62 111.8 ( 3 �97.8 ( 3 D(1,3)MU �87.7 ( 0.4c

D(1,3)ETU 15.38 ( 0.30 121.7 ( 3 �106.3 ( 3 D(1,3)EU �94.7 ( 0.3c

T(1,1,3,3)MTU 16.23 ( 0.14 84.5 ( 3 �68.3 ( 2 T(1,1,3,3)MU �90.6c

aReference 23. bReference 18. cReference 19. Uncertainties of ΔsolvHm∞ calculated by the error propagation rule.

Figure 1. Molar enthalpies of solvation at i.d. as a function of thenumber of C atoms at T = 298.15 K for thiourea and N-alkylthioureas.Values for urea andmono-, di-, tri-, and tetra-N-alkylureas are plotted forcomparison.

Table 4. Enthalpies of Solvation at Infinite Dilution in Waterof Functional Groups, ΔsolvHm

∞[FG], in Monoalkyl, 1,3-Dia-lkyl, and Tetraalkyl Derivatives of Thiourea Compared withCorresponding Urea Derivatives

ΔsolvHm∞ [FG]/ kJ 3mol�1

N-alkyl derivatives Na FG X = Sb X = Oc

monoalkyl 2 NH�CX�NH2 �81.7 �77.0

1.3-dialkyl 2 NH�CX�NH �81.0 �71.3

tetraalkyl 1 N�CX�N �35.2 �57.5a N = number of N-alkylureas. bEstimated by eq 3. cReference 19.



much less negative compared to that of the [N�CO�N]group, as expected.Partial Molar Heat Capacity. The partial molar heat capacity

at infinite dilution at T = 298.15 K, Cp,2∞ , was calculated by

summing the heat capacity change due to the solution process,ΔsolCp,m

∞ , and the molar heat capacity of pure compounds at thesame temperature:

C∞p, 2 ¼ ΔsolC

∞p, m þ Cp, mðcrÞ ð4Þ

where ΔsolCp,m∞ for thiourea and N-alkylthioureas was obtained

from the slope of eq 1:

b ¼ ð∂ΔsolH∞m =∂TÞp ¼ ΔsolC

∞p, m ð5Þ

and Cp,m(cr) values were from an earlier paper23 by some of us.It should be noted that due to this method of calculating

ΔsolCp,m∞ significant uncertainty may affect the final values of Cp,2

∞ .In our case uncertainties ofΔsolCp,m

∞ values are 8%or less.ΔsolCp,m∞ ,

Cp,m(cr), andCp,2∞ of thiourea and itsN-alkyl derivatives are given in

Table 5, columns 2 to 4, together with both the ΔsolCp,m∞ and the

Cp,2∞ values of urea and correspondingN-alkylureas, columns 6 and

7. Our ΔsolCp,m∞ for thiourea is again in excellent agreement with

the value reported by Taniewska-Osi�nska and Pazecz,29 while nodata for thioureaN-alkyl derivatives are available so far. It is worthnoting thatΔsolCp,m

∞ is positive for thiourea (19 J 3K�1

3mol�1) andnegative for urea (�19 J 3K

�13mol�1),18 whereasΔsolCp,m

∞ of bothN-alkylthioureas andN-alkylureas are all positive and progressivelylarger, the former displaying decisively higher values. It is knownthat ΔsolCp,m

∞ differentiates by sign between apolar groups(positive) and polar groups (negative).38�40 It increases uponhydrophobic hydration of apolar compounds, while the hydrationof polar compounds causes a decrease in heat capacity.41�43 Ourresults are consistent with earlier thermodynamics,16,44 dielectricspectroscopy,10 and neutron scattering8 studies, as well as mole-cular dynamics simulations9 which conclude that urea andthiourea are characterized by weak solute�solvent interactions.In addition, the opposite sign of urea and thiourea solution heatcapacity change values suggest that hydrophilic interactions arestill prevailing in urea hydration, while hydrophobic interactionsbecomes predominating in thiourea hydration. In the view of thestructure-making and structure-breakingmodel,1 we can say thaturea and thiourea oppositely act toward water structure. Thethiourea low and positive ΔsolCp,m

∞ value confirms the intrinsiclower capability of thiourea's nitrogen region to form hydrogen

bonds with water.31�33 This feature, in turn, explains the slightlyhigher Cp,2

∞ values of N-alkylthioureas.By plotting the Cp,2

∞ of N-alkylthioureas as a function of thenumber of alkyl C atoms, a slope of (88.5 ( 6.8) J 3K

�13mol

�1

was obtained, in very good agreement with that we prev-iously found for mono-, di-, tri-, and tetra-N-alkylureas,(88.9 ( 2.3) J 3 K

�13mol�1,19 (Figure 2) as well as for

N-acetylamino acid amines, (89.3 ( 0.6) J 3 K�1

3mol�1.7

Similar average Cp,2∞ [CH2] values were reported for various

monofunctional alkyl componds (89.6 J 3 K�1

3mol�1)36,45 aswell as for N-substituted alkylamides, carboxylic acids, andtheir sodium salts (90.85 J 3 K

�13mol�1).46 The increase of

Cp,2∞ in N-alkylthioureas depends on both alkyl chain length

and topography which determines a progressive increase ofwater-accessible surface area, steric hindrance of polar moi-eties, and inductive effects.47

The partial molar heat capacities of the functional groups werederived bymeans of the additive method used for evaluating theircontribution to solvation enthalpies:

C∞p, 2½FG� ¼ C∞

p, 2½N-alkylthiourea� � ∑ C∞p, 2½alkylgroup� ð6Þ

Table 5. Partial Molar Heat Capacities at Infinite Dilution, Cp,2∞ , in Water at 298.15 K for Thiourea and N-Alkylthioureas from

Equation 4

ΔsolCp,m∞ C*p,m(cr)

a Cp,2∞ ΔsolCp,m

∞ Cp,2∞ b

compound J 3K�1

3mol�1 J 3K

�13mol

�1 J 3K�1

3mol�1 compound J 3K�1

3mol�1 J 3K�1

3mol�1

TU 18.9 ( 1.5 96.2 ( 0.2 115.1 ( 1.5 U �18.95 ( 1.15b 74.2 ( 1.2b

18.6 ( 0.9c

MMTU 53.6 ( 2.6 115.4 ( 0.4 169.0 ( 2.6 MMU 27.85 ( 0.92b 143.9 ( 1.3b

METU 94.0 ( 4.9 150.4 ( 0.7 244.4 ( 4.9 MEU 75.59 ( 1.15b 227.1 ( 1.4b

D(1,3)MTU 146.0 ( 7.1 150.8 ( 0.7 296.8 ( 7.1 D(1,3)MU 136.3 ( 8d 269.6 ( 8d

D(1,3)ETU 267.4 ( 14.6 201.5 ( 0.2 468.9 ( 14.6 D(1,3)EU 233.7 ( 14d 452.7 ( 14d

T(1,1,3,3)MTU 251.7 ( 10.8 191.1 ( 0.3 442.8 ( 10.8 T(1,1,3,3)MU 171.1 ( 13d 400.7 ( 13d

aReference 24. bReference 18. cReference 29. dReference 19. Uncertainties of both ΔsolCp,m∞ and Cp,2

∞ are calculated by the error propagation rule.

Figure 2. Partial molar heat capacities at i.d. as a function of the numberof C atoms at T = 298.15 K for thiourea andN-alkylthioureas. Values forurea and mono-, di-, tri-, and tetra-N-alkylureas are plotted forcomparison.



where the partial molar heat capacitiy of themethylene group (89J 3K

�13mol

�1) is from this paper and that of the methyl group(157 J 3K

�13mol�1) is from Nichols et al.45 Results are listed in

Table 6 and compared with the values similarly obtained forN-alkylureas.18,19 The substitution of hydrogen atoms bymethylene groups progressively enhances the hydrophobicinteractions and determines a structure-making propensityproportional to the number and length of alkyl substituents inboth N-alkylureas and N-alkylthioureas. However, the lessnegative values of Cp,2

∞ [FG] inN-alkylthioureas are likely to bedue to the less hydrophilic feature of the C�N bondscompared to N-alkylureas.31�33

Finally Cp,2∞ was plotted against ΔsolvHm

∞ for both theN-alkylthioureas and theN-alkylureas18,19 (Figure 3). These valuesfall on lines with slopes of (�0.019( 0.001) K�1 and (�0.026(0.003) K�1, respectively, comparable with those given byN-acetyl substituted acid amines, (�0.023 ( 0.007) K�1,7

N-alkylamides, (�0.018 ( 0.006) K�1,3,45 dialkylsulfides,(�0.020 ( 0.004) K�1,34 alkylketones, (�0.021 ( 0.001)K�1,26,48 and n-alkan-1-ols, (�0.022( 0.002) K�1,35,45 reportedin Figure 3, too. Moreover, these slope values are comparablewith the average value found for n-alkanes, �0.022 K�1.49 Such

behavior accounts for a prevailing hydrophobic hydration thatpromotes a smaller increase in ΔsolvHm

∞ in comparison withthat of Cp,2

∞ , a parameter highly correlated with first solvationshell structure of apolar solutes.50 Polyhydric alcohols,51 bycontrast, display a much less steep plot (Figure 3) since theirstrong hydrophilic character determines a sharper increase ofΔsolvHm

∞ and a much lower Cp,2∞ increase following the alkyl

chain lengthening. It can be thus inferred that hydrophobichydration is the prevailing effect in both N-alkylureas andN-alkylthioureas.

’CONCLUSIONS

(i) The enthalpy of solvation and partial molar heat capacityat i.d. of thiourea and its mono-, di-, and tetraalkylder-ivatives display a linear dependence on the number of Catoms in the alkyl chains with slopes of ΔsolvHm

∞[CH2] =�4.5 kJ 3mol�1 and Cp,2

∞ [CH2] = 88.5 J 3K�1

3mol�1,

respectively.(ii) The enthalpies of solvation at i.d. of functional groups in

mono- and di-N-alkylthioureas are a little more exother-mic than those for urea and N-alkyureas, indicating asomewhat more efficient hydrogen bonding ability ofthionyl group compared with a carbonyl group.

(iii) A comparison between the solvation enthalpies of[N�CS�N] and [N�CO�N] functional groups con-firms the intrinsic inability of the T(1,1,3,3)TMTUnitrogen atoms to form hydrogen bonds with wateralready reported in the literature.31�33

(iv) The small, but with opposite sign, solution heat capacitychanges, ΔsolCp,m

∞ , of thiourea and urea indicate that thelatter acts as a weak water structure-breaker, whereasthiourea appears to slightly enhance the water H-bondnetwork.

(v) The large and positiveΔsolCp,m∞ values ofN-alkylthioureas

confirm they act similarly to N-alkylureas, promotingwater structuring around alkyl groups.

(vi) The interplay between partial molar heat capacity andmolar enthalpy indicate that hydrophobic interactionsprevails in N-alkylthiourea hydration as already reportedfor N-alkylureas.18

’AUTHOR INFORMATION

Corresponding Author*E-mail: [email protected]. Phone: +39 011 670 7571.Fax: +39 011 670 7855.

Funding SourcesThis work is a part of the research project “Thermodynamics ofsolvation of small model molecules”, financially supported by theItalian National Research Council (CNR). Participation of E.B.in this project was made possible by the “General Accord forCooperation and Scholar Exchange in Chemistry and Physics”between the University of Craiova (Romania) and the Universityof Turin (Italy) through a research contract. Collaboration ofM.J. in this work was rendered possible through a research grantfrom the University of Turin within the compass of a cooperationagreement with the University of y�od�z, Poland.

Notes†On leave from the University of Craiova, Faculty of Chemistry,str. Calea Bucures-ti 107 I, 200144, Craiova, Romania.

Table 6. Partial Molar Heat Capacity of the FunctionalGroups, Cp,2

∞ [FG], in Monoalkyl, 1,3-Dialkyl, and TetraalkylDerivatives of Thiourea Compared with CorrespondingN-Alkylureas

Cp,2∞ [FG]/ kJ 3mol�1

N-alkyl derivatives Na FG X = Sb X = Oc

monoalkyl 2 NH�CX�NH2 5.7 �15

1,3-dialkyl 2 NH�CX�NH �19.2 �43

tetraalkyl 1 N�CX�N �185.2 �222a N = number of N-alkylureas. b Estimated by eq 6. cReference 19.

Figure 3. Interplay between partial molar heat capacity and molarenthalpy of solvation at i.d. at T = 298.15 K forN-alkylthioureas, blueb,compared with N-alkylureas, red 2, and other series of compoundsbearing single or multiple hydrophilic functional groups: blue O,polyhydric alcohols; blue 9, N-acetylamino acid amides; purple 1, N-alkylamides; blue 0, n-alkane-1-ols; pink [, alkylketones; green f,dialkylsulfides.



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Documents

Hydration of Thiourea and Mono-, Di-, and Tetra- N -Alkylthioureas at Infinite Dilution: A Thermodynamic Study at a Temperature of 298.15 K